We have moved a DNA vaccine concept to the point of clinical testing through the IPCP funding mechanism. Our data supports that DNA vaccines can be improved by co-delivery of specific plasmid encoded cytokine adjuvants in non-human primates. This program evaluated interesting DNA Vaccine adjuvants in macaques. Results of this preclinical testing identified interleukin-12 (IL-12) and interleukin-15 (IL-15) as the most promising for clinical development. We developed substantial evidence that IL-12 can act as a highly potent DNA vaccine adjuvant in SIV infected primates for driving CTLs that appear to impact viral replication. This therapeutic study in HIV infected individuals, that was included under project 2 of the original IPCP proposal could not be completed due to delays in the manufacturing of the DNA plasmids and the additional time needed to perform the toxicity and biodistribution studies necessary to support the clinical trial. The proposed study design will test the safety and Jmmunogenicity of an optimized multigene HIV-1 DNA immunogen (PENNVAX-B) when used alone and adjuvanted with plasmid IL-12 DNA or plasmid IL-15 DNA in the context of HIV infection. Another parallel trial, conducted by the HVTN will test these products in HIV uninfected individuals.